Dr. Mary A. Bedell

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University of Georgia
Genetics
Associate ProfessorAppointed: 2004
National Institute of Health (NIH)

Mailing Address

Department of Genetics
University of Georgia
Athens, Georgia 30602
United States

Contact Information

Phone: (706) 542-0288
Fax: (706) 583-0691
bedell@uga.edu

Qualifications

Ph.D., University of Chicago, Molecular Genetics and Cell Biology, 1990.
B.A., Western Michigan University, Biomedical Sciences, 1977.

Expertise and Research Interests

Complex pathways for intercellular signaling are used in multicellular organisms to coordinate numerous aspects of development and differentiation. My laboratory studies the functions of Kit ligand (Kitl, also called stem cell factor, mast cell growth factor and Steel factor), which is the ligand for a receptor tyrosine kinase called Kit. Both Kitl and Kit are highly conserved in mammals and together make up an intercellular signaling pathway that is required for the development of germ cells, erythroid cells, mast cells and melanocytes.

In the mouse, Kitl is encoded by the Steel (Sl) locus. We have a large allelic series of Kitl^Sl mutants, including mutants that lack entire domains of Kitl, mutants that have missense substitutions in Kitl, and mutants that have defects in Kitl mRNA expression, and will use these mutants to further dissect Kitl function. Our analyses of viability and peripheral blood cells of Kitl^Sl mutant mice have revealed that several of these mutations are hypomorphic while others are null. We are using an in vitro system to examine the mechanism of altered function of a variety of Kitl mutants and preliminary results indicate that many of the Kitl^Sl mutant proteins have defects in intracellular processing. Future studies will examine further these intracellular processing defects, as well as determining the levels of surface expression of Kitl mutants, the levels of binding and activation of Kit by Kitl mutants, and in vitro bioactivity of Kitl mutants. In addition, comparative molecular modeling will be used to predict the effects of Kitl mutations on Kitl structure. Our in vivo studies of Kitl^Sl mutant mice will focus on further dissection of the requirement for Kitl during embryonic germ cell development and identification of a genetic modifier of the Kitl^Sl mutant phenotype.

Other Expertise

1992-1994, Postdoctoral Fellowship, National Institute of General Medical Sciences, NIH
1991-1992, Postdoctoral Fellowship, Foundation for Advanced Cancer Studies, Inc.
1985-1990, Lucille P. Markey Charitable Trust Award
1984-1990, Predoctoral Fellowship in Environmental Biology, Division of Biological Sciences, University of Chicago
1975, Russell H. Seibert Award, Department of Biology, Western Michigan University

REB study section, National Institutes of Health (2003-2004, ad hoc)
CMIR study section, National Institutes of Health (2004-present, regular member)

Keywords

COS Keywords:

Animal Development, Cell Lines, Cytokines, Developmental Genetics, Embryogenesis, Genetics, Molecular Biology, Molecular Cellular Entities, Molecular Genetics, Reproduction, Reproductive Biology, Signal Transduction.

Additional Terms:

Cell-cell Communication, Developmental Genetics, Hematopoiesis, Mammalian Genetics, Molecular Genetics, Signal Transduction.

Memberships

American Association for the Advancement of Science
International Mammalian Genome Society
Society for the Study of Reproduction

Previous Positions

1996-2004, Assistant Professor, University of Georgia, College of Arts and Sciences, Genetics
1990-1996, Postdoctoral Fellow, Mammalian Genetics Laboratory, ABL-BRP, NCI-FCRDC

Funding Received

  • National Institutes of Health (NIH): Growth factor control of ovarian androgen biosynthesis (D. A. Magoffin, P.I.), $99,471, Jun 1, 1999 to May 31, 2002.
  • National Science Foundation (NSF): Developmental consequences of mutations in the Steel growth factor of mice, $381,407, Jul 1, 1998 to Jun 30, 2002.
  • National Institutes of Health (NIH): Genetic analysis of Kit ligand of mice, $1,227,158, Apr 1, 2002 to May 31, 2007.

Publications

  • Zama AM, Hudson FP 3rd, Bedell MA (Oct 2005) Analysis of hypomorphic KitlSl mutants suggests different requirements for KITL in proliferation and migration of mouse primordial germ cells., Biology of Reproduction, 73 (4), 639-47 Abstract
  • Justice, M., Bedell, M. (2004) Mutagenesis of the mouse genome, Vol. Volume 2, Georgia Genetics Review, Dordrecht, The Netherlands, Kluwer Academic Publishers
  • Bedell MA, Mahakali Zama A (Mar-Apr 2004) Genetic analysis of Kit ligand functions during mouse spermatogenesis., Journal of Andrology, 25 (2), 188-99 Abstract
  • Rajaraman S, Wood LK, Willhite DK, Russell LB, Bedell MA (Mar 2003) Effects of spontaneous KitlSteel mutations on survival and red blood cells of mice., Mammalian Genome : Official Journal of the International Mammalian Genome Society., 14 (3), 168-74 Abstract
  • Rajaraman S, Davis WS, Mahakali-Zama A, Evans HK, Russell LB, Bedell MA, An Allelic Series of Mutations in the Kit ligand Gene of Mice. I. Identification of Point Mutations in Seven Ethylnitrosourea-Induced Kitl(Steel) Alleles, Genetics, 162(1), 331-40, September 2002 Abstract
  • Rajaraman S, Davis WS, Mahakali-Zama A, Evans HK, Russell LB, Bedell MA, An Allelic Series of Mutations in the Kit ligand Gene of Mice. II. Effects of Ethylnitrosourea-Induced Kitl Point Mutations on Survival and Peripheral Blood Cells of Kitl(Steel) Mice, Genetics, 162(1), 341-53, September 2002 Abstract
  • Sims JE, Williams DE, Morrissey PJ, Garka K, Foxworthe D, Price V, Friend SL, Farr A, Bedell MA, Jenkins NA, Copeland NG, Grabstein K, Paxton RJ, Molecular cloning and biological characterization of a novel murine lymphoid growth factor, Journal of Experimental Medicine, 192(5), 671-80, 2000 Abstract
  • Bedell MA, Largaespada DA, Jenkins NA, Copeland NG (Jan 1997) Mouse models of human disease. Part II: recent progress and future directions., Genes & Development, 11 (1), 11-43 Abstract
  • Bedell MA, Jenkins NA, Copeland NG (Jan 1997) Mouse models of human disease. Part I: techniques and resources for genetic analysis in mice., Genes & Development, 11 (1), 1-10 Abstract
  • Bedell MA, Jenkins NA, Copeland NG, Good genes in bad neighbourhoods., Nature Genetics, 12(3), 229-32, Mar 1996 Abstract
  • Bedell MA, Cleveland LS, O'Sullivan TN, Copeland NG, Jenkins NA (Mar 1996) Deletion and interallelic complementation analysis of Steel mutant mice., Genetics, 142 (3), 935-44 Abstract
  • Bedell MA, Copeland NG, Jenkins NA (Mar 1996) Multiple pathways for Steel regulation suggested by genomic and sequence analysis of the murine Steel gene., Genetics, 142 (3), 927-34 Abstract
  • Nagasawa M, Sakimura K, Mori KJ, Bedell MA, Copeland NG, Jenkins NA, Mishina M (Feb 1996) Gene structure and chromosomal localization of the mouse NMDA receptor channel subunits., Brain Research. Molecular Brain Research, 36 (1), 1-11 Abstract
  • Miyajima I, Levitt L, Hara T, Bedell MA, Copeland NG, Jenkins NA, Miyajima A (Mar 1995) The murine interleukin-3 receptor alpha subunit gene: chromosomal localization, genomic structure, and promoter function., Blood, 85 (5), 1246-53 Abstract
  • Bedell MA, Brannan CI, Evans EP, Copeland NG, Jenkins NA, Donovan PJ (Feb 1995) DNA rearrangements located over 100 kb 5' of the Steel (Sl)-coding region in Steel-panda and Steel-contrasted mice deregulate Sl expression and cause female sterility by disrupting ovarian follicle development., Genes & Development, 9 (4), 455-70 Abstract
  • Allen R C, Armitage R J, Conley M E, Rosenblatt H, Jenkins N A, Copeland N G, Bedell M A, Edelhoff S, Disteche C M, Simoneaux D K, et al, CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome, Science, 259(5097), 990-3, 12 Feb 1993 Abstract
  • Brannan CI, Bedell MA, Resnick JL, Eppig JJ, Handel MA, Williams DE, Lyman SD, Donovan PJ, Jenkins NA, Copeland NG (Oct 1992) Developmental abnormalities in Steel17H mice result from a splicing defect in the steel factor cytoplasmic tail., Genes & Development, 6 (10), 1832-42 Abstract
  • Brannan CI, Lyman SD, Williams DE, Eisenman J, Anderson DM, Cosman D, Bedell MA, Jenkins NA, Copeland NG (Jun 1991) Steel-Dickie mutation encodes a c-kit ligand lacking transmembrane and cytoplasmic domains., Proceedings of the National Academy of Sciences of the United States of America., 88 (11), 4671-4 Abstract
  • Bedell MA, Hudson JB, Golub TR, Turyk ME, Hosken M, Wilbanks GD, Laimins LA, Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation, Journal of Virology, 65(5), 2254-60, May 1991 Abstract
  • Rader JS, Golub TR, Hudson JB, Patel D, Bedell MA, Laimins LA, In vitro differentiation of epithelial cells from cervical neoplasias resembles in vivo lesions, Oncogene, 5(4), 571-6, April 1990 Abstract
  • Hudson JB, Bedell MA, McCance DJ, Laiminis LA, Immortalization and altered differentiation of human keratinocytes in vitro by the E6 and E7 open reading frames of human papillomavirus type 18, Journal of Virology, 64(2), 519-26, February 1990 Abstract
  • Bedell MA, Jones KH, Grossman SR, Laimins LA, Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells, Journal of Virology, 63(3), 1247-55, March 1989 Abstract
  • Gius D, Grossman S, Bedell MA, Laimins LA, Inducible and constitutive enhancer domains in the noncoding region of human papillomavirus type 18, Journal of Virology, 62(3), 665-72, March 1988 Abstract
  • Bedell MA, Jones KH, Laimins LA, The E6-E7 region of human papillomavirus type 18 is sufficient for transformation of NIH 3T3 and rat-1 cells, Journal of Virology, 61(11), 3635-40, November 1987 Abstract
  • Dyroff MC, Richardson FC, Popp JA, Bedell MA, Swenberg JA, Correlation of O4-ethyldeoxythymidine accumulation, hepatic initiation and hepatocellular carcinoma induction in rats continuously administered diethylnitrosamine, Carcinogenesis, 7(2), 241-6, February 1986 Abstract
  • Bedell MA, Dyroff MC, Doerjer G, Swenberg JA, Quantitation of etheno adducts by fluorescence detection, Iarc Scientific Publications, 425-36, 1986 Abstract
  • Swenberg JA, Dyroff MC, Bedell MA, Popp JA, Huh N, Kirstein U, Rajewsky MF, O4-ethyldeoxythymidine, but not O6-ethyldeoxyguanosine, accumulates in hepatocyte DNA of rats exposed continuously to diethylnitrosamine, Proceedings of the National Academy of Sciences (USA), 81(6), 1692-5, March 1984 Abstract
  • Lindamood C 3rd, Bedell MA, Billings KC, Dyroff MC, Swenberg JA, Dose response for DNA alkylation, [3H]thymidine uptake into DNA, and O6-methylguanine-DNA methyltransferase activity in hepatocytes of rats and mice continuously exposed to dimethylnitrosamine, Cancer Research, 44(1), 196-200, January 1984 Abstract
  • Lindamood C 3rd, Bedell MA, Billings KC, Dyroff MC, Swenberg JA, O6-alkylguanine alkyl acceptor protein activity in hepatocytes of C3H and C57BL mice during dimethylnitrosamine exposure, Chemico-biological Interactions, 45(3), 381-5, 1983 Abstract
  • Swenberg JA, Bedell MA, Billings KC, Lewis JG, Cell specificity in DNA damage and repair, Basic Life Sciences, 24, 605-17, 1983 Abstract
  • Lindamood C 3rd, Bedell MA, Billings KC, Swenberg JA, Alkylation and de novo synthesis of liver cell DNA from C3H mice during continuous dimethylnitrosamine exposure, Cancer Research, 42(10), 4153-7, October 1982 Abstract
  • Swenberg JA, Bedell MA, Billings KC, Umbenhauer DR, Pegg AE, Cell-specific differences in O6-alkylguanine DNA repair activity during continuous exposure to carcinogen, Proceedings of the National Academy of Sciences (USA), 79(18), 5499-502, September 1982 Abstract
  • Bedell MA, Lewis JG, Billings KC, Swenberg JA, Cell specificity in hepatocarcinogenesis: preferential accumulation of O6-methylguanine in target cell DNA during continuous exposure to rats to 1,2-dimethylhydrazine, Cancer Research, 42(8), 3079-83, August 1982 Abstract
  • Belinsky SA, Bedell MA, Swenberg JA, Effect of chronic ethanol diet on the replication, alkylation, and repair of DNA from hepatocytes and nonparenchymal cells following dimethylnitrosamine administration, Carcinogenesis, 3(11), 1293-7, 1982 Abstract

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